scholarly journals Autoantibodies in COVID-19 correlate with anti-viral humoral responses and distinct immune signatures

2022 ◽  
Author(s):  
Patrick Taeschler ◽  
Carlo Cervia ◽  
Yves Zurbuchen ◽  
Sara Hasler ◽  
Christian Pou ◽  
...  
Keyword(s):  
Indirect Immunofluorescence ◽  
Autoantibody Production ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Serum Proteomics ◽  
Immune Signatures ◽  
Autoimmune Pathology ◽  
Highly Sensitive ◽  
One Year ◽  
Humoral Responses

Background: Several autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. Objective: We longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID-19. Methods: We performed highly sensitive indirect immunofluorescence assays to detect anti-nuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome-wide serological profiling in a multicentric cohort of 175 COVID-19 patients followed-up to one year after infection, eleven vaccinated individuals, and 41 unexposed controls. Results: Compared to healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID-19 and recovery. However, paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID-19. Furthermore, patients with severe COVID-19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS-CoV-2-specific antibody titers in COVID-19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen-specific humoral responses. Notably, the qualitative breadth of antibodies cross-reactive with other coronaviruses was comparable in ANA-positive and ANA-negative individuals during acute COVID-19. In autoantibody-positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID-19 and alterations of the B cell compartment after recovery. Conclusion: Highly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS-CoV-2 infection, while the presence of autoantibodies in COVID-19 patients correlated with increased anti-viral humoral immune responses and inflammatory immune signatures.

scholarly journals Longitudinal immune dynamics of mild COVID-19 define signatures of recovery and persistence

2021 ◽  
Author(s):  
Aarthi Talla ◽  
Suhas V Vasaikar ◽  
Maria P Lemos ◽  
Zoe Moodie ◽  
Mark-Phillip Lee Pebworth ◽  
...  
Keyword(s):  
Immune Responses ◽  
Acute Infection ◽  
Early Time ◽  
Chromatin Accessibility ◽  
Outpatient Setting ◽  
Correlated Data ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Serum Proteomics ◽  
Humoral Responses

SARS-CoV-2 has infected over 160 million and caused more than 3 million deaths to date. Most individuals (>80%) have mild symptoms and recover in the outpatient setting, but detailed studies of immune responses have focused primarily on moderate to severe COVID-19. We deeply profiled the longitudinal immune response in individuals with mild COVID beginning with early time points post-infection (1-15 days) and proceeding through convalescence to >100 days after symptom onset. We correlated data from single cell analyses of peripheral blood cells, serum proteomics, virus-specific cellular and humoral immune responses, and clinical metadata. Acute infection was characterized by vigorous coordinated innate and adaptive activation, including an early cellular and proteomic signature that correlated with the amplitude of virus-specific humoral responses after day 30. We characterized signals associated with recovery and convalescence to define a new signature of inflammatory cytokines, gene expression, and chromatin accessibility that persists in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC).

scholarly journals Purified Hexameric Epstein-Barr Virus-Encoded BARF1 Protein for Measuring Anti-BARF1 Antibody Responses in Nasopharyngeal Carcinoma Patients

2010 ◽  
Vol 18 (2) ◽  
pp. 298-304 ◽  
Author(s):  
E. K. Hoebe ◽  
S. H. Hutajulu ◽  
J. van Beek ◽  
S. J. Stevens ◽  
D. K. Paramita ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Humoral Immune ◽  
Barr Virus ◽  
Humoral Immune Responses ◽  
Human Sera ◽  
Epstein Barr ◽  
Humoral Responses

ABSTRACTWHO type III nasopharyngeal carcinoma (NPC) is highly prevalent in Indonesia and 100% associated with Epstein-Barr virus (EBV). NPC tumor cells express viral proteins, including BARF1, which is secreted and is considered to have oncogenic and immune-modulating properties. Recently, we found conserved mutations in the BARF1 gene in NPC isolates. This study describes the expression and purification of NPC-derived BARF1 and analyzes humoral immune responses against prototype BARF1 (B95-8) and purified native hexameric BARF1 in sera of Indonesian NPC patients (n= 155) compared to healthy EBV-positive (n= 56) and EBV-negative (n= 16) individuals. BARF1 (B95-8) expressed inEscherichia coliand baculovirus, as well as BARF1-derived peptides, did not react with IgG or IgA antibodies in NPC. Purified native hexameric BARF1 protein isolated from culture medium was used in enzyme-linked immunosorbent assay (ELISA) and revealed relatively weak IgG and IgA responses in human sera, although it had strong antibody responses to other EBV proteins. Higher IgG reactivity was found in NPC patients (P= 0.015) than in regional Indonesian controls or EBV-negative individuals (P< 0.001). IgA responses to native BARF1 were marginal. NPC sera with the highest IgG responses to hexameric BARF1 in ELISA showed detectable reactivity with denatured BARF1 by immunoblotting. In conclusion, BARF1 has low immunogenicity for humoral responses and requires native conformation for antibody binding. The presence of antibodies against native BARF1 in the blood of NPC patients provides evidence that the protein is expressed and secreted as a hexameric protein in NPC patients.

scholarly journals Immunological Distinctions between Acellular and Whole-Cell Pertussis Immunizations of Baboons Persist for at Least One Year after Acellular Vaccine Boosting

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 729
Author(s):  
Leah E. Cole ◽  
Jinrong Zhang ◽  
Kristl M. Pacheco ◽  
Philippe Lhéritier ◽  
Natalie G. Anosova ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Burden ◽  
Memory B Cells ◽  
Whole Cell ◽  
Humoral Immune ◽  
Serum Bactericidal Activity ◽  
Humoral Immune Responses ◽  
Specific Memory ◽  
Antibody Titers ◽  
One Year

While both whole-cell (wP) and acellular pertussis (aP) vaccines have been highly effective at reducing the global pertussis disease burden, there are concerns that compared to wP vaccination, the immune responses to aP vaccination may wane more rapidly. To gain insights into the vaccine elicited immune responses, pre-adult baboons were immunized with either aP or wP vaccines, boosted with an aP vaccine, and observed over a nearly two-year period. Priming with a wP vaccine elicited a more Th17-biased response than priming with aP, whereas priming with an aP vaccine led to a more Th2-biased response than priming with wP. These differences were maintained after aP vaccine boost immunizations. Compared to aP, animals primed with a wP vaccine exhibited greater numbers of pertussis specific memory B cells. While aP and wP vaccine priming initially elicited similar levels of anti-pertussis toxin antibody, titers declined more rapidly in aP vaccine primed animals leading to a 4-fold difference. Both wP and aP vaccine immunization could induce serum bactericidal activity (SBA); however, only one wP vaccine immunization was required to elicit SBA while multiple aP vaccine immunizations were required to elicit lower, less durable SBA titers. In conclusion, when compared to aP vaccine, priming with wP vaccine elicits distinct cellular and humoral immune responses that persist after aP vaccine boosting.

scholarly journals Humoral protection to SARS-CoV2 declines faster in patients on TNF alpha blocking therapies

RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e002008
Author(s):  
Ulf M Geisen ◽  
Melike Sümbül ◽  
Florian Tran ◽  
Dennis K Berner ◽  
Hayley M Reid ◽  
...  
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Inflammatory Diseases ◽  
Cd4 T Cell ◽  
Vulnerable Groups ◽  
Humoral Immune ◽  
Vaccine Responses ◽  
Humoral Immune Responses ◽  
Disease Modifying ◽  
Humoral Responses

BackgroundThe persistence of the SARS-CoV2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Questions remain as to which cohorts require SARS-CoV2 boosters. However, there is a critical lack of data on the dynamics of vaccine responses in patients with chronic inflammatory diseases (CID) undergoing immunosuppressive/disease modifying anti-rheumatic (DMARD) treatment. Here, we present the first data regarding the decline of the vaccine-induced humoral immune responses in patients with CID.Methods23 patients with CID were monitored clinically and for anti-spike IgG and IgA levels, neutralization efficacy and antigen-specific CD4+ T cell responses over the first 6 months after SARS-CoV2 vaccination. 24 healthy individuals were included as controls.ResultsWhile anti-spike IgG-levels declined in CID patients and healthy controls, patients receiving anti-TNF treatment showed significantly greater declines at 6 months post second vaccination in IgG and especially neutralizing antibodies. IgA levels were generally lower in CID patients, particularly during anti-TNF therapy. No differences in SARS-CoV2 spike-specific CD4+ T-cell frequencies were detected.ConclusionAlthough the long-term efficacy of SARS-CoV2 vaccination in CID patients undergoing disease-modifying therapy is still not known, the pronounced declines in humoral responses towards SARS-CoV2 6 months after mRNA vaccination in the context of TNF blockade should be considered when formulating booster regimens. These patients should be considered for early booster vaccinations.

scholarly journals Overcoming Immunity to a Viral Vaccine by DNA Priming before Vector Boosting

2003 ◽  
Vol 77 (1) ◽  
pp. 799-803 ◽  
Author(s):  
Zhi-yong Yang ◽  
Linda S. Wyatt ◽  
Wing-pui Kong ◽  
Zoe Moodie ◽  
Bernard Moss ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Vectors ◽  
Ebola Virus ◽  
Viral Vector ◽  
Hemorrhagic Fever ◽  
Viral Immunity ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Viral Vaccine ◽  
Humoral Responses

ABSTRACT Replication-defective adenovirus (ADV) and poxvirus vectors have shown potential as vaccines for pathogens such as Ebola or human immunodeficiency virus in nonhuman primates, but prior immunity to the viral vector in humans may limit their clinical efficacy. To overcome this limitation, the effect of prior viral exposure on immune responses to Ebola virus glycoprotein (GP), shown previously to protect against lethal hemorrhagic fever in animals, was studied. Prior exposure to ADV substantially reduced the cellular and humoral immune responses to GP expressed by ADV, while exposure to vaccinia inhibited vaccine-induced cellular but not humoral responses to GP expressed by vaccinia. This inhibition was largely overcome by priming with a DNA expression vector before boosting with the viral vector. Though heterologous viral vectors for priming and boosting can also overcome this effect, the paucity of such clinical viral vectors may limit their use. In summary, it is possible to counteract prior viral immunity by priming with a nonviral, DNA vaccine.

scholarly journals Ehrlichia chaffeensis Infections in Drosophila melanogaster

2009 ◽  
Vol 77 (11) ◽  
pp. 4815-4826 ◽  
Author(s):  
Alison Luce-Fedrow ◽  
Tonia Von Ohlen ◽  
Stephen K. Chapes
Keyword(s):  
Drosophila Melanogaster ◽  
Amblyomma Americanum ◽  
Immune Defense ◽  
Ehrlichia Chaffeensis ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Defense Induction ◽  
Humoral Responses ◽  
Human Monocytic Ehrlichiosis

ABSTRACT Ehrlichia chaffeensis is an obligate, intracellular bacterium, transmitted by the tick Amblyomma americanum, and is the causative agent of human monocytic ehrlichiosis infections. We previously demonstrated that E. chaffeensis is capable of growing in Drosophila S2 cells. Therefore, we tested the hypothesis that E. chaffeensis can infect adult Drosophila melanogaster. Adult Drosophila organisms were experimentally challenged with intra-abdominal injections of bacteria. Ehrlichia-infected flies showed decreased survival compared to wild-type flies, and bacteria isolated from flies could reinfect mammalian macrophages. Ehrlichia infections activated both the cellular and humoral immune responses in the fly. Hemocytes phagocytosed bacteria after injection, and antimicrobial peptide pathways were induced following infection. Increased pathogenicity in flies carrying mutations in genes in both the Toll and Imd pathways suggests that both immune defense pathways participate in host defense. Induction of Drosophila cellular and humoral responses and the in vivo replication of E. chaffeensis suggests that D. melanogaster is a suitable host for E. chaffeensis. In the future, it will be a useful tool to unlock some of the in vivo mysteries of this arthropod-borne bacterium.

scholarly journals Humoral Immune Responses against the Mycobacteriumtuberculosis 38-Kilodalton, MTB48, and CFP-10/ESAT-6 Antigens in Tuberculosis

2010 ◽  
Vol 17 (3) ◽  
pp. 372-375 ◽  
Author(s):  
Xueqiong Wu ◽  
Yourong Yang ◽  
Junxian Zhang ◽  
Bangying Li ◽  
Yan Liang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Healthy Subjects ◽  
Enzyme Linked Immunosorbent Assay ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Single Antigen ◽  
Human Sera ◽  
Low Sensitivity ◽  
Humoral Responses ◽  
Culture Negative

ABSTRACT The diagnosis of smear-negative and culture-negative patients with active tuberculosis (TB) is challenging. The detection of Mycobacterium tuberculosis-specific antibodies in human sera has been an important diagnostic aid. However, detection of antibody responses to a single antigen usually has a low sensitivity for diagnosis of TB. In this study, humoral immune responses against recombinant M. tuberculosis 38-kDa, MTB48, and CFP-10/ESAT-6 (culture filtrate protein 10/6-kDa early secreted antigen target of M. tuberculosis) antigens in 250 Chinese TB patients and 260 healthy subjects were evaluated by an enzyme-linked immunosorbent assay (ELISA). The levels of antibodies against those antigens in TB patients, even in bacterium-negative ones, were significantly higher than those in healthy subjects (P < 0.001). The serodiagnostic sensitivities to detect antibodies against individual antigens, i.e., recombinant M. tuberculosis 38-kDa, MTB48, and CFP-10/ESAT-6 antigens, in TB patients were 73.6%, 73.2%, and 60.4%, respectively, with specificities of 85.4%, 77.7%, and 73.8%, respectively. Importantly, the sensitivity to positively detect humoral responses to one of the antigens increased further. Our data suggest that the humoral immune responses to M. tuberculosis antigens in TB patients are heterogeneous. The 38-kDa, MTB48, and CFP-10/ESAT-6 antigens can be used as the cocktail antigens in the serodiagnosis of active TB, especially for smear- or culture-negative TB cases.

scholarly journals SARS-CoV-2 Proteome-Wide Analysis Revealed Significant Epitope Signatures in COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Tatjana Schwarz ◽  
Kirsten Heiss ◽  
Yuvaraj Mahendran ◽  
Fiordiligie Casilag ◽  
Florian Kurth ◽  
...  
Keyword(s):  
Viral Infections ◽  
Severe Disease ◽  
Severe Pneumonia ◽  
Asymptomatic Infection ◽  
Disease Outcome ◽  
Humoral Immune ◽  
Peptide Microarrays ◽  
Humoral Immune Responses ◽  
Longitudinal Approach ◽  
Humoral Responses

The WHO declared the COVID-19 outbreak a public health emergency of international concern. The causative agent of this acute respiratory disease is a newly emerged coronavirus, named SARS-CoV-2, which originated in China in late 2019. Exposure to SARS−CoV−2 leads to multifaceted disease outcomes from asymptomatic infection to severe pneumonia, acute respiratory distress and potentially death. Understanding the host immune response is crucial for the development of interventional strategies. Humoral responses play an important role in defending viral infections and are therefore of particular interest. With the aim to resolve SARS-CoV-2-specific humoral immune responses at the epitope level, we screened clinically well-characterized sera from COVID-19 patients with mild and severe disease outcome using high-density peptide microarrays covering the entire proteome of SARS-CoV-2. Moreover, we determined the longevity of epitope-specific antibody responses in a longitudinal approach. Here we present IgG and IgA-specific epitope signatures from COVID-19 patients, which may serve as discriminating prognostic or predictive markers for disease outcome and/or could be relevant for intervention strategies.

scholarly journals IgA dominates the early neutralizing antibody response to SARS-CoV-2

2020 ◽  
pp. eabd2223 ◽  
Author(s):  
Delphine Sterlin ◽  
Alexis Mathian ◽  
Makoto Miyara ◽  
Audrey Mohr ◽  
François Anna ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Immune Memory ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Virus Specific Antibody ◽  
Iga Response ◽  
Humoral Responses ◽  
Antibody Secreting Cells

Humoral immune responses are typically characterized by primary IgM antibody responses followed by secondary antibody responses associated with immune memory and comprised of of IgG, IgA and IgE. Here we measured acute humoral responses to SARS-CoV-2, including the frequency of antibody-secreting cells and the presence of SARS-CoV-2-specific neutralizing antibodies in the serum, saliva and broncho-alveolar fluid of 159 patients with COVID-19. Early SARS-CoV-2-specific humoral responses were dominated by IgA antibodies. Peripheral expansion of IgA plasmablasts with mucosal-homing potential was detected shortly after the onset of symptoms and peaked during the third week of the disease. The virus-specific antibody responses included IgG, IgM and IgA, but IgA contributed to virus neutralization to a greater extent compared with IgG. Specific IgA serum concentrations decreased notably one month after the onset of symptoms, but neutralizing IgA remained detectable in saliva for a longer time (days 49 to 73 post symptoms). These results represent a critical observation given the emerging information as to the types of antibodies associated with optimal protection against re-infection, and whether vaccine regimens should consider targeting a potent but potentially short-lived IgA response.

scholarly journals Strong humoral immune responses against SARS-CoV-2 Spike after BNT162b2 mRNA vaccination with a sixteen-week interval between doses

2021 ◽  
Author(s):  
Alexandra Tauzin ◽  
Shang Yu Gong ◽  
Guillaume Beaudoin-Bussieres ◽  
Dani Vezina ◽  
Romain Gasser ◽  
...  
Keyword(s):  
Public Health ◽  
Immune Responses ◽  
Vaccine Efficacy ◽  
Standard Regimen ◽  
Effector Functions ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Health Authorities ◽  
Public Health Authorities ◽  
Humoral Responses

While the standard regimen of the BNT162b2 mRNA vaccine includes two doses administered three weeks apart, some public health authorities decided to space them, raising concerns about vaccine efficacy. Here, we analyzed longitudinal humoral responses including antibody binding, Fc-mediated effector functions and neutralizing activity against the D614G strain but also variants of concern and SARS-CoV-1 in a cohort of SARS-CoV-2 naive and previously infected individuals, with an interval of sixteen weeks between the two doses. While the administration of a second dose to previously infected individuals did not significantly improve humoral responses, we observed a significant increase of humoral responses in naive individuals after the 16-weeks delayed second shot, achieving similar levels as in previously infected individuals. Our results highlight strong vaccine-elicited humoral responses with an extended interval BNT162b2 vaccination for naive individuals.

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